The following publications are relevant for describing the state of the art in the field of the invention    1. L. Hanus, et al. Proc. Natl. Acad. Sci, U.S.A. 96:14228-14233, 1999.    2. O. Ofek, et al. Proc. Natl. Acad. Sci. U.S.A. 103:696-701, 2006.    3. I. Bab, et al. J. Neuroendocrinol. 20 Suppl 1:69-74, 2008.    4. L. Hanus, et al. Org. Biomol. Chem. 3:1116-1123, 2005.    5. W. A. Devane, et al. Science. 258:1946-1949, 1992.    6. S. Munro, et al. Nature. 365:61-65, 1993.    7. S. M. Miguel, et al. J. Biol. Chem. 280:37495-37502, 2005.    8. J. M. Alexander, et al. J. Bone Min. Res. 16:1665-1673, 2001.    9. I. Bab, et al. WO 2004/103,410    10. E. Fride et al. U.S. Pat. No. 6,864,291    11. R. Mechoulam et al. U.S. Pat. No. 5,434,295
In vertebrates, skeletal mass is determined by continuous remodeling consisting of the concerted and balanced action of osteoclasts, the bone resorbing cells, and osteoblasts, the bone forming cells.
Osteoporosis, the most prevalent degenerative disease in developed countries, results from the impairment of this balance, leading to bone loss and increased fracture risk. We have recently reported the expression of functional type 2 cannabinoid receptor (CB2) in bone cells.
The CB2 specific agonist HU-308 (WO 2004/103410; Hanu{hacek over (s)} et al, 1999), stimulates in vitro osteoblastogenesis and inhibits osteoclastogenesis. In mice, HU-308 stimulates bone formation and inhibits bone resorption, thus attenuating ovariectomy (OVX)-induced bone loss (Ofek et al, 2006). In another mouse model it rescues OVX-induced bone loss (Bab et al, 2008).